tbuckley/cabot-search huggingface dataset:
Association of In-person vs Virtual Education With Community COVID-19 Case Incidence Following School Reopenings in the First Year of the COVID-19 Pandemic
Authors: Meredith Matone, Xi Wang, Deanna Marshall, Jing Huang, Diana Worsley, Corinne Filograna, David Rubin
Journal: JAMA Network Open (2023)

The variability in timing of middle and secondary school reopenings during the 2020 to 2021 school year in the US presents an opportunity to examine the associations of different approaches to in-person education with changes in community COVID-19 incidence. Early studies on this topic have reached mixed conclusions and may be biased by unmeasured confounders.To estimate the association of in-person vs virtual instruction for students at the sixth grade level or above with county-level COVID-19 incidence in the first year of the COVID-19 pandemic.This cohort study included matched pairs of counties resuming school programs with in-person vs virtual instruction, drawn from 229 US counties that contained a single public school district and with county populations exceeding 100 000 residents. Counties that contained 1 single public school district and reopened in-person schooling for students at the sixth grade level or above during the fall of 2020 were matched 1-to-1 with counties whose school district reopened with only virtual instruction, based on geographic proximity, population-level demographic factors, the resumption of school district-level fall sports activity, and baseline county COVID-19 incidence rates. Data were analyzed from November 2021 to November 2022.In-person instruction for students at the sixth grade level or above resuming between August 1 and October 31, 2020.County-level daily COVID-19 incidence per 100 000 residents.The inclusion criteria and subsequent matching algorithm led to the identification of 51 pairs of matched counties among 79 total unique counties. Exposed counties had a median (IQR) of 141 840 (81 441-241 910) residents each, and unexposed counties had a median (IQR) of 131 412 (89 011-278 666) residents each. County schools with in-person vs virtual instruction had similar daily COVID-19 case incidence within the first 4 weeks after in-person reopening, but counties with in-person instruction had higher daily incidence beyond 4 weeks. Daily case incidence per 100 000 residents among counties with in-person instruction, compared with counties with virtual instruction, was higher at 6 weeks (adjusted incidence rate ratio, 1.24 [95% CI, 1.00-1.55]) and at 8 weeks after (adjusted incidence rate ratio, 1.31 [95% CI, 1.06-1.62]). This outcome was also concentrated in counties where schools provided full rather than hybrid instructional models.In a cohort study of matched pairs of counties that reopened with in-person vs virtual instruction at the secondary school level in the 2020 to 2021 academic year, counties with in-person school instructional models early in the COVID-19 pandemic experienced increases in county-level COVID-19 incidence at 6 and 8 weeks after in-person reopening, compared with counties with virtual instructional models.
A Novel Patient‐Personalized Nanovector Based on Homotypic Recognition and Magnetic Hyperthermia for an Efficient Treatment of Glioblastoma Multiforme
Authors: Daniele De Pasquale, Carlotta Pucci, Andrea Desii, Attilio Marino, Doriana Debellis, Luca Leoncino, Mirko Prato, Stefania Moscato, Simone Amadio, Pietro Fiaschi, Alessandro Prior, Gianni Ciofani
Journal: Advanced Healthcare Materials (2023)

Glioblastoma multiforme (GBM) is the deadliest brain tumor, characterized by an extreme genotypic and phenotypic variability, besides a high infiltrative nature in healthy tissues. Apart from very invasive surgical procedures, to date, there are no effective treatments, and life expectancy is very limited. In this work, an innovative therapeutic approach based on lipid-based magnetic nanovectors is proposed, owning a dual therapeutic function: chemotherapy, thanks to an antineoplastic drug (regorafenib) loaded in the core, and localized magnetic hyperthermia, thanks to the presence of iron oxide nanoparticles, remotely activated by an alternating magnetic field. The drug is selected based on ad hoc patient-specific screenings; moreover, the nanovector is decorated with cell membranes derived from patients' cells, aiming at increasing homotypic and personalized targeting. It is demonstrated that this functionalization not only enhances the selectivity of the nanovectors toward patient-derived GBM cells, but also their blood-brain barrier in vitro crossing ability. The localized magnetic hyperthermia induces both thermal and oxidative intracellular stress that lead to lysosomal membrane permeabilization and to the release of proteolytic enzymes into the cytosol. Collected results show that hyperthermia and chemotherapy work in synergy to reduce GBM cell invasion properties, to induce intracellular damage and, eventually, to prompt cellular death.
DNA-Methylome–Based Tumor Hypoxia Classifier Identifies HPV-Negative Head and Neck Cancer Patients at Risk for Locoregional Recurrence after Primary Radiochemotherapy
Authors: Bouchra Tawk, Katrin Rein, Christian Schwager, Maximilian Knoll, Ute Wirkner, Juliane Hörner-Rieber, Jakob Liermann, Ina Kurth, Panagiotis Balermpas, Claus Rödel, Annett Linge, Steffen Löck, Fabian Lohaus, Ingeborg Tinhofer, Mechtild Krause, Martin Stuschke, Anca Ligia Grosu, Daniel Zips, Stephanie E. Combs, Claus Belka, Albrecht Stenzinger, Christel Herold-Mende, Michael Baumann, Peter Schirmacher, Jürgen Debus, Amir Abdollahi
Journal: Clinical Cancer Research (2023)

Tumor hypoxia is a paradigmatic negative prognosticator of treatment resistance in head and neck squamous cell carcinoma (HNSCC). The lack of robust and reliable hypoxia classifiers limits the adaptation of stratified therapies. We hypothesized that the tumor DNA methylation landscape might indicate epigenetic reprogramming induced by chronic intratumoral hypoxia.A DNA-methylome-based tumor hypoxia classifier (Hypoxia-M) was trained in the TCGA (The Cancer Genome Atlas)-HNSCC cohort based on matched assignments using gene expression-based signatures of hypoxia (Hypoxia-GES). Hypoxia-M was validated in a multicenter DKTK-ROG trial consisting of human papillomavirus (HPV)-negative patients with HNSCC treated with primary radiochemotherapy (RCHT).Although hypoxia-GES failed to stratify patients in the DKTK-ROG, Hypoxia-M was independently prognostic for local recurrence (HR, 4.3; P = 0.001) and overall survival (HR, 2.34; P = 0.03) but not distant metastasis after RCHT in both cohorts. Hypoxia-M status was inversely associated with CD8 T-cell infiltration in both cohorts. Hypoxia-M was further prognostic in the TCGA-PanCancer cohort (HR, 1.83; P = 0.04), underscoring the breadth of this classifier for predicting tumor hypoxia status.Our findings highlight an unexplored avenue for DNA methylation-based classifiers as biomarkers of tumoral hypoxia for identifying high-risk features in patients with HNSCC tumors. See related commentary by Heft Neal and Brenner, p. 2954.
Abdominal Pain and Petechial Rash in a 95-Year-Old Farmer
Authors: Rino Kadekaru, Hiroyuki Yano, Mitsuyo Kinjo
Journal: JAMA (2023)

A 95-year-old farmer taking prednisolone for bullous pemphigoid had 24 hours of abdominal pain, 2 weeks of diarrhea, and 3 months of intermittent abdominal bloating and anorexia. Evaluation showed purpuric macules and small thumbprint-like patches on her upper abdomen and central chest and a white blood cell count of 13 600/μL (89.9% neutrophils, 0.2% eosinophils). What is the diagnosis and what would you do next?
Primary papillary epithelial tumor of the sella and posterior pituitary tumor show similar (epi)genetic features and constitute a single neuro-oncological entity
Authors: Jing Feng, Zejun Duan, Kun Yao, Qiuping Gui, Xing Liu, Xingfu Wang, Zunguo Du, Liwei Shao, Benyan Zhang, Shanshan Cai, Mingwang Zhu, Zhong Ma, Zejuan Hu, Lei Xiang, Xiaolong Fan, Xueling Qi
Journal: Neuro-Oncology (2023)

"Primary papillary epithelial tumor of the sella (PPETS)" is a recently described rare tumor entity of the central nervous system (CNS) with stereotypic location in the sella. Comprehensive molecular investigations and epigenetic profiles of PPETS have not been performed to date.We report a comprehensive clinical, histopathologic, and molecular assessment of 5 PPETS cases in comparison with a cohort composed of 7 choroid plexus papilloma (CPP), 7 central neurocytoma (CN), 15 posterior pituitary tumor (PPT) including 4 pituicytoma, 6 granular cell tumors of the sellar region (GCT), and 5 spindle cell oncocytoma.All PPETS had good outcomes. Immunohistochemically, PPETS tumors showed positive staining with TTF1, EMA, AE1/AE3, MAP2, and Vimentin, but were negatively stained with Syn, GFAP, CgA, and S100, and sporadically stained with Ki-67. In unsupervised hierarchical clustering and t-distributed stochastic neighbor embedding analyses of DNA-methylation data, PPETS and PPT tumors formed a distinct cluster irrespective of their histologic types. However, PPETS tumors did not cluster together with CPP and CN samples. Similar findings were obtained when our samples were projected into the reference cohort of the brain tumor classifier. Substantial fractions of the PPETS and PPT tumors shared broadly similar chromosomal copy number alterations. No mutations were detected using targeted next-generation sequencing.Though more cases are needed to further elucidate the molecular pathogenesis of these tumors, our findings indicate that PPETS and PPT tumors may constitute a single neurooncological entity.
Therapeutic modulation of the liver immune microenvironment
Authors: Herbert Tilg, Timon E. Adolph, Frank Tacke
Journal: Hepatology (2023)

Inflammation is a hallmark of progressive liver diseases such as chronic viral or immune-mediated hepatitis, alcohol-associated liver disease, and NAFLD. Preclinical and clinical studies have provided robust evidence that cytokines and related cellular stress sensors in innate and adaptive immunity orchestrate hepatic disease processes. Unresolved inflammation and liver injury result in hepatic scarring, fibrosis, and cirrhosis, which may culminate in HCC. Liver diseases are accompanied by gut dysbiosis and a bloom of pathobionts, fueling hepatic inflammation. Anti-inflammatory strategies are extensively used to treat human immune-mediated conditions beyond the liver, while evidence for immunomodulatory therapies and cell therapy–based strategies in liver diseases is only emerging. The development and establishment of novel immunomodulatory therapies for chronic liver diseases has been dampened by several clinical challenges, such as invasive monitoring of therapeutic efficacy with liver biopsy in clinical trials and risk of DILI in several studies. Such aspects prevented advancements of novel medical therapies for chronic inflammatory liver diseases. New concepts modulating the liver immune environment are studied and eagerly awaited to improve the management of chronic liver diseases in the future.
Shared Risk Factors for Depressive Disorder Among Older Adult Couples in Korea
Authors: Ji Won Han, Hee Won Yang, Jong Bin Bae, Dae Jong Oh, Dong Gyu Moon, Eunji Lim, Jin Shin, Bong Jo Kim, Dong Woo Lee, Jeong Lan Kim, Jin Hyeong Jhoo, Joon Hyuk Park, Jung Jae Lee, Kyung Phil Kwak, Seok Bum Lee, Seok Woo Moon, Seung-Ho Ryu, Shin Gyeom Kim, Ki Woong Kim
Journal: JAMA Network Open (2023)

Importance Although couples may share many risk factors for depressive disorders in their lifetime, whether these factors mediate the shared risk of depressive disorders has rarely been investigated. Objectives To identify the shared risk factors for depressive disorder in couples and investigate their mediating roles in the shared risk of depressive disorders among older adult couples. Design, Setting, and Participants This nationwide, multicenter, community-based cohort study assessed 956 older adults from the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) and a cohort of their spouses (KLOSCAD-S) between January 1, 2019, to February 28, 2021. Exposures Depressive disorders of the KLOSCAD participants. Main Outcomes and Measures The mediating roles of shared factors in couples on the association between one spouse’s depressive disorder and the other’s risk of depressive disorders was examined using structural equation modeling. Results A total of 956 KLOSCAD participants (385 women [40.3%] and 571 men [59.7%]; mean [SD] age, 75.1 [5.0] years) and their spouses (571 women [59.7%] and 385 men [40.3%]; mean [SD] age, 73.9 [6.1] years) were included. The depressive disorders of the KLOSCAD participants were associated with an almost 4-fold higher risk of depressive disorders in their spouses in the KLOSCAD-S cohort (odds ratio, 3.89; 95% CI, 2.06-7.19; P &amp;amp;lt; .001). Social-emotional support mediated the association between depressive disorders in the KLOSCAD participants and their spouses’ risk of depressive disorders by itself (β = 0.012; 95% CI, 0.001-0.024; P = .04; mediation proportion [MP] = 6.1%) and through chronic illness burden (β = 0.003; 95% CI, 0.000-0.006; P = .04; MP = 1.5%). Chronic medical illness burden (β = 0.025; 95% CI, 0.001-0.050; P = .04; MP = 12.6%) and presence of a cognitive disorder (β = 0.027; 95% CI, 0.003-0.051; P = .03; MP = 13.6%) mediated the association. Conclusions and Relevance The risk factors shared by older adult couples may mediate approximately one-third of the spousal risk of depressive disorders. Identification of and intervention in the shared risk factors of depression among older adult couples may reduce the risk of depressive disorders in the spouses of older adults with depression.
Identifying Electronic Health Record Contributions to Diagnostic Error in Ambulatory Settings Through Legal Claims Analysis
Authors: Seth A. Krevat, Sunil Samuel, Christian Boxley, Vishnu Mohan, Dana Siegal, Jeffrey A. Gold, Raj M. Ratwani
Journal: JAMA Network Open (2023)

This qualitative study analyzes closed legal claims data to determine whether problems with electronic health records are associated with diagnostic errors, in which part of the diagnostic process errors occur, and the specific types of errors that occur.
Comparing early life nutritional sources and human milk feeding practices: personalized and dynamic nutrition supports infant gut microbiome development and immune system maturation
Authors: Spencer R. Ames, Larisa C. Lotoski, Meghan B. Azad
Journal: Gut Microbes (2023)

Exclusive breastfeeding is recommended for the first six months of life, but many infants receive pumped milk, formula, donor human milk, or other nutritional sources during this critical period. Substantive evidence shows early nutrition influences development of the microbiome and immune system, affecting lifelong health. However, the underlying mechanisms are unclear and the nuances of human milk feeding are rarely considered. This review synthesizes evidence from human studies and model systems to discuss the impact of different nutritional sources on co-development of the gut microbiome, antigen tolerance, and immunity. We highlight two key mechanisms: epigenetics and the so-called "weaning reaction". Collectively, this evidence highlights i) the fundamental role of parents' own milk, fed directly at the breast, as a dynamic and personalized nutrition source that drives developmental programming, and ii) the deficiencies of alternative nutritional sources and priority research areas for improving these alternatives when direct breastfeeding is not possible.
Effect of regional versus general anesthesia on thirty-day outcomes following carotid endarterectomy: a cohort study
Authors: Leigh A. Kline, Venkatraman Kothandaraman, Ziyad O. Knio, Zhiyi Zuo
Journal: International Journal of Surgery (2023)

The effect of regional versus general anesthesia on carotid endarterectomy outcomes is debated. This study assesses the effect of anesthetic technique on major morbidity and mortality and additional secondary endpoints following carotid endarterectomy.This was a retrospective propensity-matched-cohort analysis investigating elective carotid endarterectomy patients in the 2015-2019 American College of Surgeons National Surgical Quality Improvement Program ( n =37 204). The primary endpoint was 30-day mortality and major morbidity, defined as stroke, myocardial infarction, or death. Secondary endpoints included minor morbidity, bleeding events, healthcare resource utilization, and length of hospital stay. Univariate, multivariable, and survival analyses were applied.The 1 : 1 propensity-matched-cohort included 8304 patients (4152 in each group). Regional anesthesia was associated with similar incidences of major morbidity and mortality [odds ratio (OR), 0.81 (95% CI, 0.61-1.09); P = 0.162] and unplanned resource utilization [OR, 0.93 (95% CI, 0.78-1.11); P = 0.443], but lower incidences of minor morbidity [OR, 0.60 (95% CI, 0.44-0.81); P < 0.001] and bleeding events [OR, 0.49 (95% CI, 0.30-0.78); P = 0.002], and a shorter length of hospital stay [1.4 vs. 1.6 days; mean difference, -0.16 days (95% CI, -0.25 to -0.07); P < 0.001]. On multivariable analysis, regional anesthesia remained independently predictive of minor morbidity [adjusted odds ratio (AOR), 0.58 (95% CI, 0.42-0.79); P = 0.001] and bleeding events [AOR, 0.49 (95% CI, 0.30-0.77); P = 0.003]. Significance was maintained on survival analysis for these two endpoints. A mortality benefit was observed on univariate [OR, 0.50 (95% CI, 0.25-1.00); P = 0.045], multivariable [AOR, 0.49 (95% CI, 0.24-0.96); P = 0.043], and survival analysis ( P = 0.045).Carotid endarterectomy patients receiving regional anesthesia experience favorable outcomes compared to propensity-matched general anesthesia controls.
TONSL Is an Immortalizing Oncogene and a Therapeutic Target in Breast Cancer
Authors: Aditi S. Khatpe, Rebecca Dirks, Poornima Bhat-Nakshatri, Henry Mang, Katie Batic, Sarah Swiezy, Jacob Olson, Xi Rao, Yue Wang, Hiromi Tanaka, Sheng Liu, Jun Wan, Duojiao Chen, Yunlong Liu, Fang Fang, Sandra Althouse, Emily Hulsey, Maggie M. Granatir, Rebekah Addison, Constance J. Temm, George Sandusky, Audrey Lee-Gosselin, Kenneth Nephew, Kathy D. Miller, Harikrishna Nakshatri
Journal: Cancer Research (2023)

Study of genomic aberrations leading to immortalization of epithelial cells has been technically challenging due to the lack of isogenic models. To address this, we used healthy primary breast luminal epithelial cells of different genetic ancestry and their hTERT-immortalized counterparts to identify transcriptomic changes associated with immortalization. Elevated expression of TONSL (Tonsoku-like, DNA repair protein) was identified as one of the earliest events during immortalization. TONSL, which is located on chromosome 8q24.3, was found to be amplified in approximately 20% of breast cancers. TONSL alone immortalized primary breast epithelial cells and increased telomerase activity, but overexpression was insufficient for neoplastic transformation. However, TONSL-immortalized primary cells overexpressing defined oncogenes generated estrogen receptor-positive adenocarcinomas in mice. Analysis of a breast tumor microarray with approximately 600 tumors revealed poor overall and progression-free survival of patients with TONSL-overexpressing tumors. TONSL increased chromatin accessibility to pro-oncogenic transcription factors, including NF-κB and limited access to the tumor-suppressor p53. TONSL overexpression resulted in significant changes in the expression of genes associated with DNA repair hubs, including upregulation of several genes in the homologous recombination (HR) and Fanconi anemia pathways. Consistent with these results, TONSL-overexpressing primary cells exhibited upregulated DNA repair via HR. Moreover, TONSL was essential for growth of TONSL-amplified breast cancer cell lines in vivo, and these cells were sensitive to TONSL-FACT complex inhibitor CBL0137. Together, these findings identify TONSL as a regulator of epithelial cell immortalization to facilitate cancer initiation and as a target for breast cancer therapy.The chr.8q24.3 amplicon-resident gene TONSL is upregulated during the initial steps of tumorigenesis to support neoplastic transformation by increasing DNA repair and represents a potential therapeutic target for treating breast cancer.
Uptake of Maintenance Immunotherapy and Changes in Upstream Treatment Selection Among Patients With Urothelial Cancer
Authors: Ronac Mamtani, Hanxi Zhang, Ravi B. Parikh, Khilna Patel, Haojie Li, Kentaro Imai, Rebecca A. Hubbard
Journal: JAMA Network Open (2023)

This cohort study compares the proportion of patients with urothelual cancer who initiated first-line chemotherapy and immune checkpoint inhibitors during the periods before and after avelumab approval.
Outcomes after microsurgical treatment of lymphedema: a systematic review and meta-analysis
Authors: Joachim N. Meuli, Martino Guiotto, Jolanda Elmers, Lucia Mazzolai, Pietro G. di Summa
Journal: International Journal of Surgery (2023)

Microsurgical treatment options for lymphedema consist mainly of lymphovenous anastomosis (LVA) and vascularized lymph node transfers (VLNTs). There are no standard measurements of the effectiveness of these interventions and reported outcomes vary among studies.A systematic review and meta-analysis were performed based on a structured search in Embase, Medline, PubMed, Cinahl, Cochrane, and ProQuest in October 2020, with an update in February 2022. Firstly, a qualitative summary of the main reported outcomes was performed, followed by a pooled meta-analysis of the three most frequently reported outcomes using a random effects model. Randomized controlled trials, prospective cohorts, retrospective cohorts, and cross-sectional and case-control studies that documented outcomes following microsurgery in adult patients were included. Studies of other surgical treatments (liposuction, radical excision, lymphatic vessel transplantation) or without reported outcomes were excluded. The study protocol was registered on PROSPERO (International Prospective Register of Systematic Reviews) (ID: CRD42020202417). No external funding was received for this review.One hundred fifty studies, including 6496 patients, were included in the systematic review. The qualitative analysis highlighted the three most frequently reported outcomes: change in circumference, change in volume, and change in the number of infectious episodes per year. The overall pooled change in excess circumference across 29 studies, including 1002 patients, was -35.6% [95% CI: -30.8 to -40.3]. The overall pooled change in excess volume across 12 studies including 587 patients was -32.7% [95% CI: -19.8 to -45.6], and the overall pooled change in the number of cutaneous infections episodes per year across 8 studies including 248 patients was -1.9 [95% CI: -1.4 to -2.3]. The vast majority of the studies included were case series and cohorts, which were intrinsically exposed to a risk of selection bias.The currently available evidence supports LVA and vascularized lymph node transfers as effective treatments to reduce the severity of secondary lymphedema. Standardization of staging method, outcomes measurements, and reporting is paramount in future research in order to allow comparability across studies and pooling of results.